Universal cancer vaccine

ABSTRACT

Described herein are compositions of matter and methods for treating cancer. The compositions comprise altered human telomerase polypeptides containing T cell epitopes that have been altered to increase immunogenicity. The methods comprise administration of the polypeptides or nucleic acids, such as DNA or RNA encoding the polypeptides, to individuals afflicted with, or at risk of, developing cancer.

CROSS REFERENCE

This application claims priority to U.S. Application Ser. No. 62/298,956filed on Feb. 23, 2016; 62/320,440 filed on Apr. 8, 2016; and 62/341,771filed on May 26, 2016; all of which are incorporated herein in theirentirety.

BACKGROUND

Human telomerase reverse transcriptase (TERT) is a constitutiveself-tumor antigen and a potential target for cancer immunotherapy. Inthe past immunotherapy trials targeting TERT have failed to deliver onthe promise of TERT as an immunotherapy target. For example, of 25clinical studies performed using TERT as an antigen to induce ananti-tumor immune response, an objective clinical response has beenshown in only 2 studies, and even then, with an overall response rate ofless than 20%.

Telomerase reverse transcriptase (TERT) is a component of telomerase,the unique cellular enzyme that synthesizes the tandem 5′-TTAGGG-3′exonucleotide repeats of telomeric DNA by reverse transcription of itsown RNA template (TERC). The discovery of telomerase andtelomerase-mediated extension of telomeric DNA solved both theend-replication problem, i.e., the mechanism by which telomeric DNA ismaintained, and the end-protection problem. Human TERT is a self-antigenthat consists of ˜1130 amino acids. In humans, telomerase activity bythe canonical telomeric repeat amplification protocol (TRAP) assay isdetected in >85% of tumors of various histological type, but not innormal tissues.

Tolerance is one major determinant in the development of one'sindividual immune response, and a major obstacle to developimmunotherapy to self-antigens such as telomerase. During ontogeny,tolerance shapes the repertoire by eliminating high affinity T cellprecursors and sparing low affinity T cell precursors. Tumor growth canalso promote peripheral tolerance if antigen-presenting cells activate Tcells in the absence of costimulatory molecules (signal 2). In addition,certain T cell specificities may be lost over time due to senescence andexhaustion, or by remodeling cancer cell immunogenicity by immuneediting.

Cellular responses to antigen by B and T cells are largely dictated bythe human leukocyte antigens (HLA) present on an individual's cellsurface. Intracellular antigens (e.g., viral proteins, self-proteins)are processed intracellularly, generally by the proteasome, to yield8-10 amino acid polypeptides. 8-10-mers are loaded onto MHC class I HLAsubtype A, B and C molecules for presentation to cytotoxic CD 8⁺ Tcells. These cytotoxic T cells can then recognize and destroy cellscarrying organisms (e.g., viruses) that express the protein. There arethousands of different HLA alleles split between the A, B and, C locus.These alleles are grouped into different types with designations such asA2 or B44. Some types are more common than others, with the A2 typebeing the most prevalent.

SUMMARY

Telomerase is expressed at many stages of tumor development, as shown inFIG. 1. Additionally, telomerase promoter mutations are seen in manydifferent cancer types. See FIG. 2. Thus telomerase is an attractivetarget for therapeutic intervention including, among others, vaccinationwith the polypeptides described herein. Alternatively, T cells can bestimulated ex vivo or in vivo by antigen presenting cells loaded with Tcell response epitopes derived form the altered human telomerasepolypeptides described herein. By altering a low affinity T cell epitopeto promote binding to a particular HLA as shown in FIG. 3A it ispossible to circumvent the problem of tolerance as previously described.FIG. 3B illustrates that this approach is feasible for a polypeptidecorresponding to SEQ ID NO: 13 which substitutes an arginine fortyrosine mutation at p1 of the polypeptide that binds to HLA-A2(position 572 of wild type telomerase).

Referring to FIGS. 4 and 5 (two different not limiting schematics of analtered human telomerase polypeptide), telomerase possess severalpotential HLA binding polypeptides (rectangles) that can be altered(black squares) to bind to HLA with a much stronger affinity than thewild type version. If administered with a T cell helper epitope(diamonds), e.g., by engineering such an epitope into the alteredtelomerase, the altered telomerase peptides can induce a CD8⁺ T cellresponse. Because these peptides originally bind to various HLA alleleswith low to medium affinity the endogenous CD 8⁺ T cell repertoireagainst them is not yet tolerized. Administering an altered telomerasethat has one or more altered polypeptides will activate and expand theseuntolerized T cells leading to an immune response to telomeraseexpressing (e.g., cancer) cells.

Described herein, are compositions and methods useful for theimmunotherapy of cancer using altered telomerase or altered telomerasepolypeptides as an antigen. The compositions are useful because theybreak tolerance to the self-antigen telomerase, and because they arecapable of prompting a response in individuals of differing HLAhaplotype. In certain embodiments, the composition comprises one or moreHLA binding polypeptides, derived from human telomerase, which have beenaltered from their naturally occurring sequence to impart increasedimmunogenicity. These altered polypeptides are generally subdominant,and as such, T cells responsive to them have not been tolerized. Incertain embodiments, the polypeptides are administered separately or asa single larger polypeptide. In certain, embodiments, the polypeptidesare administered with a T helper epitope, adjuvant, or ligand for aninnate immune activating molecule, such as a Toll-like receptor (TLR) orNOD-like receptor (NLR). Also described herein, are nucleic acids thatencode telomerase and T helper cell polypeptides including RNAs.

In certain embodiments, described herein is, a polypeptide comprising atleast one sequence of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ IDNO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10,SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15,SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20,SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25,SEQ ID NO: 26, or SEQ ID NO: 27. In certain embodiments, the polypeptidecomprises at least two different sequences of SEQ ID NO:2, SEQ ID NO:3,SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ IDNO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ IDNO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ IDNO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ IDNO: 24, SEQ ID NO: 25, SEQ ID NO: 26, or SEQ ID NO: 27. In certainembodiments, the polypeptide comprises at least three differentsequences of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21,SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,or SEQ ID NO: 27. In certain embodiments, the polypeptide comprises atleast five different sequences of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4,SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ IDNO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ IDNO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ IDNO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ IDNO: 25, SEQ ID NO: 26, or SEQ ID NO: 27. In certain embodiments, thepolypeptide comprises at least ten different sequences of SEQ ID NO:2,SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ IDNO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ IDNO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ IDNO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ IDNO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, or SEQ ID NO: 27. Incertain embodiments, the polypeptide comprises at least seven differentsequences of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21,SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,or SEQ ID NO: 27, wherein each of the seven different sequences binds adifferent human leukocyte antigen selected from the group consisting ofA1, A2, A3, A11, A24, B3, B7 and B44. In certain embodiments, thepolypeptide comprises a non-human T cell helper epitope, wherein thenon-human T cell helper epitope binds more than one human class II HLAtype. In certain embodiments, the T cell helper epitope comprisestetanus toxoid. In certain embodiments, the T cell helper epitope isselected from the group consisting of SEQ ID NO: 30 to SEQ ID NO: 55,and combinations thereof. In certain embodiments, the T cell helperepitope is set forth in SEQ ID NO: 30. In certain embodiments, thepolypeptide comprises a total length of at least 20 amino acids. Incertain embodiments, the polypeptide comprises a total length of atleast 50 amino acids. In certain embodiments, the polypeptide comprisesa total length of at least 100 amino acids. In certain embodiments, anucleic acid molecule encodes the polypeptide. In certain embodiments, acomplex comprising at least 8 contiguous amino acids of the polypeptideis bound to a cell surface human leukocyte antigen of an antigenpresenting cell. In certain embodiments, the antigen presenting cell isa B cell. In certain embodiments, the antigen presenting cell is adendritic cell. In certain embodiments, described herein, is acomposition that comprises the polypeptide and an immunologicaladjuvant. In certain embodiments, described herein, is a compositionthat comprises the polypeptide and a Toll-like receptor ligand. Incertain embodiments, described herein, is a composition that comprisesthe polypeptide and a pharmaceutically acceptable vehicle, carrier,excipient, or a combination thereof. In certain embodiments, describedherein, is a composition that comprises the polypeptide and a non-humanT cell helper epitope, wherein the non-human T cell helper epitope bindsmore than one human class II HLA type. In certain embodiments, the Tcell helper epitope comprises tetanus toxoid. In certain embodiments,the T cell helper epitope is selected from the group consisting of SEQID NO: 30 to SEQ ID NO: 55, and combinations thereof. In certainembodiments, the T cell helper epitope is set forth in SEQ ID NO: 30.

In another embodiment, described herein, is an altered human telomerasepolypeptide with at least 90% identity to the sequence set forth in SEQID NO: 1, wherein the altered human telomerase polypeptide comprises atleast one amino acid substitution that is at position R19, L22, R132,L152, D444, K492, E555, L556, T564, R572, R577, D637, L675, E727, R742,T765, R811, L840, G847, T874, L940, K981, V997, or P1020. In certainembodiments, the altered human telomerase polypeptide is at least 95%identical to SEQ ID NO: 1. In certain embodiments, the altered humantelomerase polypeptide comprises at least two amino acid substitutionsthat are at positions R19, L22, R132, L152, D444, K492, E555, L556,T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847, T874,L940, K981, V997, or P1020. In certain embodiments, the altered humantelomerase polypeptide comprises at least three amino acid substitutionsthat are at positions R19, L22, R132, L152, D444, K492, E555, L556,T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847, T874,L940, K981, V997, or P1020. In certain embodiments, the altered humantelomerase polypeptide comprises at least five amino acid substitutionsthat are at positions R19, L22, R132, L152, D444, K492, E555, L556,T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847, T874,L940, K981, V997, or P1020. In certain embodiments, the altered humantelomerase polypeptide comprises at least ten amino acid substitutionsthat are at positions R19, L22, R132, L152, D444, K492, E555, L556,T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847, T874,L940, K981, V997, or P1020. In certain embodiments, at least one aminoacid substitution increases the binding affinity of an 8 to 10 aminoacid polypeptide derived from the altered human telomerase polypeptideto at least one human leukocyte antigen of an A, B, or C type by atleast two-fold. In certain embodiments, at least one amino acidsubstitution increases the binding affinity of an 8 to 10 amino acidpolypeptide derived from the altered human telomerase polypeptide to atleast one human leukocyte antigen of an A, B, or C type by at leastfive-fold. In certain embodiments, at least one amino acid substitutionincreases the binding affinity of an 8 to 10 amino acid polypeptidederived from the altered human telomerase polypeptide to at least onehuman leukocyte antigen of an A, B, or C type by at least ten-fold. Incertain embodiments, the altered human telomerase polypeptide comprisesan insertion of a non-human T cell helper epitope into the polypeptidesequence of the altered human telomerase, wherein the non-human T cellhelper epitope binds more than one human class II HLA type. In certainembodiments, the T cell helper epitope comprises tetanus toxoid. Incertain embodiments, the T cell helper epitope is selected from thegroup consisting of SEQ ID NO: 30 to SEQ ID NO: 55, and combinationsthereof. In certain embodiments, the T cell helper epitope is set forthin SEQ ID NO: 30. In certain embodiments, a nucleic acid moleculeencodes the altered human telomerase polypeptide. In certainembodiments, a complex comprising at least 8 contiguous amino acids ofthe altered human telomerase polypeptide is bound to a cell surfacehuman leukocyte antigen of an antigen presenting cell. In certainembodiments, the antigen presenting cell is a B cell. In certainembodiments, the antigen presenting cell is a dendritic cell. In certainembodiments, described herein, is a composition that comprises thealtered human telomerase polypeptide and an immunological adjuvant. Incertain embodiments, described herein, is a composition that comprisesthe altered human telomerase polypeptide and a Toll-like receptorligand. In certain embodiments, described herein, is a composition thatcomprises the altered human telomerase polypeptide and apharmaceutically acceptable vehicle, carrier, excipient, or acombination thereof. In certain embodiments, described herein, is acomposition that comprises the altered human telomerase polypeptide anda non-human T cell helper epitope, wherein the non-human T cell helperepitope binds more than one human class II HLA type. In certainembodiments, the T cell helper epitope comprises tetanus toxoid. Incertain embodiments, the T cell helper epitope is selected from thegroup consisting of SEQ ID NO: 30 to SEQ ID NO: 55, and combinationsthereof. In certain embodiments, the T cell helper epitope is set forthin SEQ ID NO: 30.

In another embodiment, described herein, is an altered human telomerasepolypeptide with at least 90% identity to the sequence set forth in SEQID NOs: 28 or 29, wherein the altered human telomerase polypeptide isnot identical to SEQ ID NO: 1. In certain embodiments, the altered humantelomerase polypeptide is at least 95% identical to SEQ ID NO: 28 or 29.In certain embodiments, the altered human telomerase polypeptide is atleast 98% identical to SEQ ID NO: 28 or 29. In certain embodiments, thealtered human telomerase polypeptide is at least 99% identical to SEQ IDNO: 28 or 29. In certain embodiments, the altered human telomerasepolypeptide is at least 100% identical to SEQ ID NO: 28 or 29. Incertain embodiments, the altered telomerase polypeptide increases thebinding affinity of an 8-10 amino acid polypeptide derived from thealtered human telomerase polypeptide to at least one human leukocyteantigen of the A, B, or C type by at least two-fold. In certainembodiments, the at least one amino acid alteration increases thebinding affinity of an 8-10 amino acid polypeptide derived from thealtered human telomerase polypeptide to at least one human leukocyteantigen of the A, B, or C type by at least five-fold. In certainembodiments, the at least one amino acid alteration increases thebinding affinity of an 8-10 amino acid polypeptide derived from thealtered human telomerase polypeptide to at least one human leukocyteantigen of the A, B, or C type by at least ten-fold. In certainembodiments, the altered human telomerase polypeptide comprises aninsertion of a non-human T cell helper epitope into the polypeptidesequence of the altered human telomerase, wherein the non-human T cellhelper epitope binds more than one human class II HLA type. In certainembodiments, the T cell helper epitope is selected from the groupconsisting of SEQ ID NO: 30 to SEQ ID NO: 55, and combinations thereof.In certain embodiments, the T cell helper epitope is set forth in SEQ IDNO: 30. In certain embodiments, a nucleic acid molecule encodes thealtered human telomerase polypeptide. In certain embodiments, a complexcomprising at least 8 contiguous amino acids of the altered humantelomerase polypeptide is bound to a cell surface human leukocyteantigen of an antigen presenting cell. In certain embodiments, theantigen presenting cell is a B cell. In certain embodiments, the antigenpresenting cell is a dendritic cell. In certain embodiments, describedherein, is a composition that comprises the altered human telomerasepolypeptide and an immunological adjuvant. In certain embodiments,described herein, is a composition that comprises the altered humantelomerase polypeptide and a Toll-like receptor ligand. In certainembodiments, described herein, is a composition that comprises thealtered human telomerase polypeptide and a pharmaceutically acceptablevehicle, carrier, excipient, or a combination thereof. In certainembodiments, described herein, is a composition that comprises thealtered human telomerase polypeptide and a non-human T cell helperepitope, wherein the non-human T cell helper epitope binds more than onehuman class II HLA type. In certain embodiments, the T cell helperepitope comprises tetanus toxoid. In certain embodiments, the T cellhelper epitope is selected from the group consisting of SEQ ID NO: 30 toSEQ ID NO: 55, and combinations thereof. In certain embodiments, the Tcell helper epitope is set forth in SEQ ID NO: 30.

In certain embodiments, described herein, is a method for treating anindividual with cancer the method comprising administering to anindividual with cancer a polypeptide comprising at least one sequence ofSEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, or SEQID NO: 27. In certain embodiments, the polypeptide comprises at leasttwo different sequences of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ IDNO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10,SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15,SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20,SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25,SEQ ID NO: 26, or SEQ ID NO: 27. In certain embodiments, the polypeptidecomprises at least three different sequences of SEQ ID NO:2, SEQ IDNO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8,SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ IDNO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ IDNO: 24, SEQ ID NO: 25, SEQ ID NO: 26, or SEQ ID NO: 27. In certainembodiments, the polypeptide comprises at least five different sequencesof SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, or SEQID NO: 27. In certain embodiments, the polypeptide comprises at leastten different sequences of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ IDNO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10,SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15,SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20,SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25,SEQ ID NO: 26, or SEQ ID NO: 27. In certain embodiments, the polypeptidecomprises at least seven different sequences of SEQ ID NO:2, SEQ IDNO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8,SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ IDNO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ IDNO: 24, SEQ ID NO: 25, SEQ ID NO: 26, or SEQ ID NO: 27, wherein each ofthe seven different sequences binds a different human leukocyte antigenselected from the group consisting of A1, A2, A3, A11, A24, B3, B7 andB44. In certain embodiments, the polypeptide comprises a non-humanpolypeptide comprising a T cell helper epitope, wherein the non-human Tcell helper epitope binds more than one human class II HLA type. Incertain embodiments, the T cell helper epitope is selected from thegroup consisting of SEQ ID NO: 30 to SEQ ID NO: 55, and combinationsthereof. In certain embodiments, the T cell helper epitope is set forthin SEQ ID NO: 30. In certain embodiments, the polypeptide comprises atotal length of at least 20 amino acids. In certain embodiments, thepolypeptide comprises a total length of at least 50 amino acids. Incertain embodiments, the polypeptide comprises a total length of atleast 100 amino acids. In certain embodiments, a nucleic acid moleculeis administered that encodes the polypeptide. In certain embodiments,the method comprises administering a complex comprising at least 8contiguous amino acids of the polypeptide bound to a cell surface humanleukocyte antigen of an antigen presenting cell. In certain embodiments,the antigen presenting cell is a B cell. In certain embodiments, theantigen presenting cell is a dendritic cell. In certain embodiments, themethod further comprises administering an immunological adjuvant. Incertain embodiments, the method further comprises administering aToll-like receptor ligand. In certain embodiments, the method furthercomprises administering a pharmaceutically acceptable vehicle, carrier,excipient, or a combination thereof. In certain embodiments, the canceris of hematological origin. In certain embodiments, the individual inneed has a telomerase positive cancer. In certain embodiments, thecancer is selected from the group consisting of bladder cancer, livercancer, glioblastoma, melanoma, prostate cancer, a cancer of the thymus,cancer of the thyroid, and kidney cancer. In certain embodiments, themethod further comprises administering a non-human T cell helperepitope. In certain embodiments, the T cell helper epitope is selectedfrom the group consisting of SEQ ID NO: 30 to SEQ ID NO: 55, andcombinations thereof. In certain embodiments, the T cell helper epitopeis set forth in SEQ ID NO: 30.

In certain embodiments, described herein, is a method for treating anindividual with cancer comprising administering to an individual withcancer an altered human telomerase polypeptide with at least 90%identity to the sequence set forth in SEQ ID NO: 1, wherein the alteredhuman telomerase polypeptide comprises at least one amino acidsubstitution that is at position R19, L22, R132, L152, D444, K492, E555,L556, T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847,T874, L940, K981, V997, or P1020. In certain embodiments, the alteredhuman telomerase polypeptide is at least 95% identical to SEQ ID NO: 1.In certain embodiments, the altered human telomerase polypeptidecomprises at least two amino acid substitutions that are at positionsR19, L22, R132, L152, D444, K492, E555, L556, T564, R572, R577, D637,L675, E727, R742, T765, R811, L840, G847, T874, L940, K981, V997, orP1020. In certain embodiments, the altered human telomerase polypeptidecomprises at least three amino acid substitutions that are at positionsR19, L22, R132, L152, D444, K492, E555, L556, T564, R572, R577, D637,L675, E727, R742, T765, R811, L840, G847, T874, L940, K981, V997, orP1020. In certain embodiments, the altered human telomerase polypeptidecomprises at least five amino acid substitutions that are at positionsR19, L22, R132, L152, D444, K492, E555, L556, T564, R572, R577, D637,L675, E727, R742, T765, R811, L840, G847, T874, L940, K981, V997, orP1020. In certain embodiments, the altered human telomerase polypeptidecomprises at least ten amino acid substitutions that are at positionsR19, L22, R132, L152, D444, K492, E555, L556, T564, R572, R577, D637,L675, E727, R742, T765, R811, L840, G847, T874, L940, K981, V997, orP1020. In certain embodiments, the at least one amino acid substitutionincreases the binding affinity of an 8-10 amino acid polypeptide derivedfrom the altered human telomerase polypeptide to at least one humanleukocyte antigen of an A, B, or C type by at least two-fold. In certainembodiments, the at least one amino acid substitution increases thebinding affinity of an 8-10 amino acid polypeptide derived from thealtered human telomerase polypeptide to at least one human leukocyteantigen of an A, B, or C type by at least five-fold. In certainembodiments, the at least one amino acid substitution increases thebinding affinity of an 8-10 amino acid polypeptide derived from thealtered human telomerase polypeptide to at least one human leukocyteantigen of an A, B, or C type by at least ten-fold. In certainembodiments, the altered human telomerase polypeptide comprises aninsertion of a non-human T cell helper epitope into the polypeptidesequence of the altered human telomerase, wherein the non-human T cellhelper epitope binds more than one human class II HLA type. In certainembodiments, the T cell helper epitope is selected from the groupconsisting of SEQ ID NO: 30 to SEQ ID NO: 55, and combinations thereof,wherein the non-human T cell helper epitope binds more than one humanclass II HLA type. In certain embodiments, the T cell helper epitope isset forth in SEQ ID NO: 30. In certain embodiments, a nucleic acidmolecule is administered that encodes the altered human telomerasepolypeptide. In certain embodiments, the method comprises administeringa complex comprising at least 8 contiguous amino acids of thepolypeptide bound to a cell surface human leukocyte antigen of anantigen presenting cell. In certain embodiments, the antigen presentingcell is a B cell. In certain embodiments, the antigen presenting cell isa dendritic cell. In certain embodiments, the method further comprisesadministering an immunological adjuvant. In certain embodiments, themethod further comprises administering a Toll-like receptor ligand. Incertain embodiments, the method further comprises administering apharmaceutically acceptable vehicle, carrier, excipient, or acombination thereof. In certain embodiments, the cancer is ofhematological origin. In certain embodiments, the individual in need hasa telomerase positive cancer. In certain embodiments, the cancer isselected from the group consisting of bladder cancer, liver cancer,glioblastoma, melanoma, prostate cancer, a cancer of the thymus, cancerof the thyroid, and kidney cancer. In certain embodiments, the methodfurther comprises administering a non-human T cell helper epitope. Incertain embodiments, the T cell helper epitope is selected from thegroup consisting of SEQ ID NO: 30 to SEQ ID NO: 55, and combinationsthereof. In certain embodiments, the T cell helper epitope is set forthin SEQ ID NO: 30.

In certain embodiments, described herein, is a method for treating anindividual with cancer the method comprising administering to theindividual with cancer an altered human telomerase polypeptide at least90% identical to SEQ ID NO: 28 or 29, wherein the altered humantelomerase polypeptide is not identical to SEQ ID NO: 1. In certainembodiments, the altered human telomerase polypeptide is at least 95%identical to SEQ ID NO: 28 or 29. In certain embodiments, the alteredhuman telomerase polypeptide is at least 98% identical to SEQ ID NO: 28or 29. In certain embodiments, the altered human telomerase polypeptideis at least 99% identical to SEQ ID NO: 28 or 29. In certainembodiments, the altered human telomerase polypeptide is at least 100%identical to SEQ ID NO: 28 or 29. In certain embodiments, the alteredtelomerase polypeptide increases the binding affinity of an 8-10 aminoacid polypeptide derived from the altered human telomerase polypeptideto at least one human leukocyte antigen of the A, B, or C type by atleast two-fold. In certain embodiments, the at least one amino acidalteration increases the binding affinity of an 8-10 amino acidpolypeptide derived from the altered human telomerase polypeptide to atleast one human leukocyte antigen of the A, B, or C type by at leastfive-fold. In certain embodiments, the at least one amino acidalteration increases the binding affinity of an 8-10 amino acidpolypeptide derived from the altered human telomerase polypeptide to atleast one human leukocyte antigen of the A, B, or C type by at leastten-fold. In certain embodiments, the altered human telomerasepolypeptide comprises an insertion of a non-human polypeptide comprisinga T cell helper epitope into the polypeptide sequence of the alteredhuman telomerase, wherein the non-human T cell helper epitope binds morethan one human class II HLA type. In certain embodiments, the T cellhelper epitope is selected from the group consisting of SEQ ID NO: 30 toSEQ ID NO: 55, and combinations thereof. In certain embodiments, the Tcell helper epitope is set forth in SEQ ID NO: 30. In certainembodiments, a nucleic acid molecule is administered that encodes thealtered human telomerase polypeptide. In certain embodiments, the methodcomprises administering a complex comprising at least 8 contiguous aminoacids of the polypeptide bound to a cell surface human leukocyte antigenof an antigen presenting cell. In certain embodiments, the antigenpresenting cell is a B cell. In certain embodiments, the antigenpresenting cell is a dendritic cell. In certain embodiments, the methodfurther comprises administering an immunological adjuvant. In certainembodiments, the method further comprises administering a Toll-likereceptor ligand. In certain embodiments, the method further comprisesadministering a pharmaceutically acceptable vehicle, carrier, excipient,or a combination thereof. In certain embodiments, the cancer is ofhematological origin. In certain embodiments, the individual in need hasa telomerase positive cancer. In certain embodiments, the cancer isselected from the group consisting of bladder cancer, liver cancer,glioblastoma, melanoma, prostate cancer, a cancer of the thymus, cancerof the thyroid, and kidney cancer. In certain embodiments, the methodfurther comprises administering a non-human T cell helper epitope. Incertain embodiments, the T cell helper epitope is selected from thegroup consisting of SEQ ID NO: 30 to SEQ ID NO: 55, and combinationsthereof. In certain embodiments, the T cell helper epitope is set forthin SEQ ID NO: 30.

In certain embodiments, described herein, is a method of preparing acancer treatment the method comprising admixing a polypeptide comprisingat least one sequence of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ IDNO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10,SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15,SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20,SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25,SEQ ID NO: 26, or SEQ ID NO: 27, and a pharmaceutically acceptablevehicle, carrier, excipient, or combination thereof. In certainembodiments, the polypeptide comprises at least two different sequencesof SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, or SEQID NO: 27. In certain embodiments, the polypeptide comprises at leastthree different sequences of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ IDNO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ IDNO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ IDNO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ IDNO: 25, SEQ ID NO: 26, or SEQ ID NO: 27. In certain embodiments, thepolypeptide comprises at least five different sequences of SEQ ID NO:2,SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ IDNO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ IDNO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ IDNO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ IDNO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, or SEQ ID NO: 27. Incertain embodiments, the polypeptide comprises at least ten differentsequences of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21,SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,or SEQ ID NO: 27. In certain embodiments, the polypeptide comprises atleast seven different sequences of SEQ ID NO:2, SEQ ID NO:3, SEQ IDNO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9,SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14,SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19,SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24,SEQ ID NO: 25, SEQ ID NO: 26, or SEQ ID NO: 27, wherein each of theseven different sequences binds a different human leukocyte antigenselected from the group consisting of A1, A2, A3, A11, A24, B3, B7 andB44. In certain embodiments, the polypeptide comprises a non-human Tcell helper epitope, wherein the non-human T cell helper epitope bindsmore than one human class II HLA type. In certain embodiments, the Tcell helper epitope is selected from the group consisting of SEQ ID NO:30 to SEQ ID NO: 55, and combinations thereof. In certain embodiments,the T cell helper epitope is set forth in SEQ ID NO: 30. In certainembodiments, the polypeptide comprises a total length of at least 20amino acids. In certain embodiments, the polypeptide comprises a totallength of at least 50 amino acids. In certain embodiments, thepolypeptide comprises a total length of at least 100 amino acids. Incertain embodiments, the method comprises admixing a nucleic acidmolecule encoding the polypeptide, and a pharmaceutically acceptablevehicle, carrier, excipient, or combination thereof. In certainembodiments, the method comprises admixing a complex comprising at least8 contiguous amino acids of the polypeptide bound to a cell surfacehuman leukocyte antigen of an antigen presenting cell, and apharmaceutically acceptable vehicle, carrier, excipient, or combinationthereof. In certain embodiments, the antigen presenting cell is a Bcell. In certain embodiments, the antigen presenting cell is a dendriticcell. In certain embodiments, the treatment further comprises admixingan immunological adjuvant. In certain embodiments, the treatment furthercomprises admixing a Toll-like receptor ligand. In certain embodiments,the treatment further comprises admixing a non-human a T cell helperepitope. In certain embodiments, the T cell helper epitope is selectedfrom the group consisting of SEQ ID NO: 30 to SEQ ID NO: 55, andcombinations thereof, wherein the non-human T cell helper epitope bindsmore than one human class II HLA type. In certain embodiments, the Tcell helper epitope is set forth in SEQ ID NO: 30.

In certain embodiments, described herein, is a method of preparing acancer treatment the method comprising admixing a composition comprisingan altered human telomerase polypeptide with at least 90% identity tothat set forth in SEQ ID NO: 1, comprising at least one amino acidsubstitution that is at position R19, L22, R132, L152, D444, K492, E555,L556, T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847,T874, L940, K981, V997, or P1020, and a pharmaceutically acceptablevehicle, carrier, excipient, or combination thereof. In certainembodiments, the altered human telomerase polypeptide is at least 95%identical to SEQ ID NO: 1. In certain embodiments, the altered humantelomerase polypeptide comprises at least two amino acid substitutionsthat are at positions R19, L22, R132, L152, D444, K492, E555, L556,T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847, T874,L940, K981, V997, or P1020. In certain embodiments, the altered humantelomerase polypeptide comprises at least three amino acid substitutionsthat are at positions R19, L22, R132, L152, D444, K492, E555, L556,T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847, T874,L940, K981, V997, or P1020. In certain embodiments, the altered humantelomerase polypeptide comprises at least five amino acid substitutionsthat are at positions R19, L22, R132, L152, D444, K492, E555, L556,T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847, T874,L940, K981, V997, or P1020. In certain embodiments, the altered humantelomerase polypeptide comprises at least ten amino acid substitutionsthat are at positions R19, L22, R132, L152, D444, K492, E555, L556,T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847, T874,L940, K981, V997, or P1020. In certain embodiments, the at least oneamino acid substitution increases the binding affinity of an 8 to 10amino acid polypeptide derived from the altered human telomerasepolypeptide to at least one human leukocyte antigen of an A, B, or Ctype by at least two-fold. In certain embodiments, the at least oneamino acid substitution increases the binding affinity of an 8 to 10amino acid polypeptide derived from the altered human telomerasepolypeptide to at least one human leukocyte antigen of an A, B, or Ctype by at least five-fold. In certain embodiments, the at least oneamino acid substitution increases the binding affinity of an 8 to 10amino acid polypeptide derived from the altered human telomerasepolypeptide to at least one human leukocyte antigen of an A, B, or Ctype by at least ten-fold. In certain embodiments, the altered humantelomerase polypeptide comprises an insertion of a non-human T cellhelper epitope into the polypeptide sequence of the altered humantelomerase, wherein the non-human T cell helper epitope binds more thanone human class II HLA type. In certain embodiments, the T cell helperepitope is selected from the group consisting of SEQ ID NO: 30 to SEQ IDNO: 55, and combinations thereof. In certain embodiments, the T cellhelper epitope is set forth in SEQ ID NO: 30. In certain embodiments,the method comprises admixing a nucleic acid molecule encoding thealtered human telomerase polypeptide, and a pharmaceutically acceptablevehicle, carrier, excipient, or combination thereof. In certainembodiments, the method comprises admixing a complex comprising at least8 contiguous amino acids of the polypeptide bound to a cell surfacehuman leukocyte antigen of an antigen presenting cell, and apharmaceutically acceptable vehicle, carrier, excipient, or combinationthereof. In certain embodiments, the antigen presenting cell is a Bcell. In certain embodiments, the antigen presenting cell is a dendriticcell. In certain embodiments, the treatment further comprises admixingan immunological adjuvant. In certain embodiments, the treatment furthercomprises admixing a Toll-like receptor ligand. In certain embodiments,the treatment further comprises admixing a non-human a T cell helperepitope. In certain embodiments, the T cell helper epitope is selectedfrom the group consisting of SEQ ID NO: 30 to SEQ ID NO: 55, andcombinations thereof, wherein the non-human T cell helper epitope bindsmore than one human class II HLA type. In certain embodiments, the Tcell helper epitope is set forth in SEQ ID NO: 30.

In certain embodiments, described herein, is a method of preparing acancer treatment the method comprising admixing an altered humantelomerase polypeptide at least 90% identical to SEQ ID NO: 28 or 29,wherein the altered human telomerase polypeptide is not identical to SEQID NO: 1 and a pharmaceutically acceptable vehicle, carrier, excipient,or combination thereof. In certain embodiments, the altered humantelomerase polypeptide is at least 95% identical to SEQ ID NO: 28 or 29.In certain embodiments, the altered human telomerase polypeptide is atleast 98% identical to SEQ ID NO: 28 or 29. In certain embodiments, thealtered human telomerase polypeptide is at least 99% identical to SEQ IDNO: 28 or 29. In certain embodiments, the altered human telomerasepolypeptide is at least 100% identical to SEQ ID NO: 28 or 29. Incertain embodiments, the altered telomerase polypeptide increases thebinding affinity of an 8 to 10 amino acid polypeptide derived from thealtered human telomerase polypeptide to v the at least one amino acidalteration increases the binding affinity of an 8 to 10 amino acidpolypeptide derived from the altered human telomerase polypeptide to atleast one human leukocyte antigen of the A, B, or C type by at leastfive-fold. In certain embodiments, the at least one amino acidalteration increases the binding affinity of an 8 to 10 amino acidpolypeptide derived from the altered human telomerase polypeptide to atleast one human leukocyte antigen of the A, B, or C type by at leastten-fold. In certain embodiments, the altered human telomerasepolypeptide comprises an insertion of a non-human polypeptide comprisinga T cell helper epitope into the polypeptide sequence of the alteredhuman telomerase, wherein the non-human T cell helper epitope binds morethan one human class II HLA type. In certain embodiments, the T cellhelper epitope is selected from the group consisting of SEQ ID NO: 30 toSEQ ID NO: 55, and combinations thereof. In certain embodiments, the Tcell helper epitope is set forth in SEQ ID NO: 30. In certainembodiments, the method comprises admixing a nucleic acid moleculeencoding the altered human telomerase polypeptide, and apharmaceutically acceptable vehicle, carrier, excipient, or combinationthereof. In certain embodiments, the method comprises admixing a complexcomprising at least 8 contiguous amino acids of the polypeptide bound toa cell surface human leukocyte antigen of an antigen presenting cell,and a pharmaceutically acceptable vehicle, carrier, excipient, orcombination thereof In certain embodiments, the antigen presenting cellis a B cell. In certain embodiments, the antigen presenting cell is adendritic cell. In certain embodiments, the treatment further comprisesadmixing an immunological adjuvant. In certain embodiments, thetreatment further comprises admixing a Toll-like receptor ligand. Incertain embodiments, the treatment further comprises admixing anon-human a T cell helper epitope. In certain embodiments, the T cellhelper epitope is selected from the group consisting of SEQ ID NO: 30 toSEQ ID NO: 55, and combinations thereof, wherein the non-human T cellhelper epitope binds more than one human class II HLA type. In certainembodiments, the T cell helper epitope is set forth in SEQ ID NO: 30.

In certain embodiments, described herein, is a method of treating cancercomprising transfecting an antigen presenting cell ex vivo with anucleic acid that encodes a polypeptide of any of SEQ ID NO:2, SEQ IDNO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8,SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ IDNO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ IDNO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, orSEQ ID NO: 29. In certain embodiments, the antigen presenting cell is aB cell. In certain embodiments, the antigen presenting cell is adendritic cell.

In certain embodiments, described herein, is a method of treating cancercomprising administering an antigen presenting cell that has beentransfected ex vivo with a nucleic acid that encodes a polypeptide ofany of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6,SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ IDNO: 27, SEQ ID NO: 28, or SEQ ID NO: 29. In certain embodiments, theantigen presenting cell is a B cell. In certain embodiments, the antigenpresenting cell is a dendritic cell. In certain embodiments, greaterthan 1×10⁶ cells are administered. In certain embodiments, the cells areadministered intravenously.

In a certain aspect provided herein, is a polypeptide comprising atleast two sequences set forth in any one of SEQ ID NO:2, SEQ ID NO:3,SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ IDNO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ IDNO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ IDNO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ IDNO: 24, SEQ ID NO: 25, SEQ ID NO: 26, or SEQ ID NO: 27. In certainembodiments, the polypeptide comprises at least seven differentsequences of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21,SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,or SEQ ID NO: 27, wherein each of the seven different sequences binds adifferent human leukocyte antigen selected from the group consisting ofA1, A2, A3, A11, A24, B3, B7, and B44. In certain embodiments, thepolypeptide comprises a non-human T cell helper epitope, wherein thenon-human T cell helper epitope binds more than one human class II HLAtype. In certain embodiments, the polypeptide comprises a total lengthof at least 20 amino acids. In certain embodiments, the polypeptide isencoded by a polynucleotide. In certain embodiments, the polynucleotidecomprises ribonucleic acid (RNA). In certain embodiments, at least eightcontiguous amino acids of the polypeptide is bound to a cell surfacehuman leukocyte antigen of an antigen presenting cell. In certainembodiments, the polypeptide further comprises an immunologicaladjuvant. In certain embodiments, the polypeptide further comprises apharmaceutically acceptable vehicle, carrier or excipient. In certainembodiments, the polypeptide is for use in treating an individual withcancer.

In a certain aspect provided herein, is an altered human telomerasepolypeptide with at least 90% identity to the sequence set forth in SEQID NO: 1, wherein the altered human telomerase polypeptide comprises atleast one amino acid substitution that is at position R19, L22, R132,L152, D444, K492, E555, L556, T564, R572, R577, D637, L675, E727, R742,T765, R811, L840, G847, T874, L940, K981, V997, or P1020. In certainembodiments, the altered human telomerase polypeptide comprises aninsertion of a non-human T cell helper epitope into the polypeptidesequence of the altered human telomerase, wherein the non-human T cellhelper epitope binds more than one human class II HLA type. In certainembodiments, the altered human telomerase polypeptide is encoded by apolynucleotide. In certain embodiments, the altered human telomerasepolynucleotide comprises ribonucleic acid (RNA). In certain embodiments,at least eight contiguous amino acids of the altered human telomerasepolypeptide is bound to a cell surface human leukocyte antigen of anantigen presenting cell. In certain embodiments, the altered humantelomerase polypeptide further comprises an immunological adjuvant. Incertain embodiments, the altered human telomerase polypeptide furthercomprises a pharmaceutically acceptable vehicle, carrier or excipient.In certain embodiments, the altered human telomerase polypeptide is foruse in treating an individual with cancer.

In a certain aspect provided herein, is an altered human telomerasepolypeptide with at least 90% identity to the sequence set forth in anyone of SEQ ID NOs: 28 or 29, wherein the altered human telomerasepolypeptide is not identical to SEQ ID NO: 1.In certain embodiments, thealtered human telomerase polypeptide comprises an insertion of anon-human T cell helper epitope into the polypeptide sequence of thealtered human telomerase, wherein the non-human T cell helper epitopebinds more than one human class II HLA type. In certain embodiments, thealtered human telomerase polypeptide is encoded by a polynucleotide. Incertain embodiments, the altered human telomerase polynucleotidecomprises ribonucleic acid (RNA). In certain embodiments, at least eightcontiguous amino acids of the altered human telomerase polypeptide isbound to a cell surface human leukocyte antigen of an antigen presentingcell. In certain embodiments, the altered human telomerase polypeptidefurther comprises an immunological adjuvant. In certain embodiments, thealtered human telomerase polypeptide further comprises apharmaceutically acceptable vehicle, carrier or excipient. In certainembodiments, the altered human telomerase polypeptide is for use intreating an individual with cancer.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic showing that telomerase is expressed at manydifferent stage of cancer progression.

FIG. 2 is a diagram showing that many different types of cancers arecaused by mutations in the telomerase promotor.

FIG. 3A shows a graphical depiction illustrating that peptides thatnaturally bind MHC Class I HLA subtypes with low affinity possess a Tcell repertoire that has not been deleted or tolerized.

FIG. 3B shows flow cytometry data of tetramer staining of peripheralblood mononuclear cells. This data shows that immunization with analtered peptide can expand a CD 8+ T cell repertoire that cross reactswith the naturally occurring peptide.

FIG. 4 is a non-limiting schematic of an altered telomerase peptide,depicting a plurality of altered epitopes, and an integrated non-human Tcell helper epitope able to bind a plurality of human MHC class II HLAtypes.

FIG. 5 is a second non-limiting schematic of an altered telomerasepeptide, depicting a plurality of altered epitopes, and an integratednon-human T cell helper epitope able to bind a plurality of human MHCclass II HLA types.

DETAILED DESCRIPTION OF THE INVENTION

Described herein, in certain embodiments, is a polypeptide comprising atleast one sequence of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ IDNO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10,SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15,SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20,SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25,SEQ ID NO: 26, or SEQ ID NO: 27.

Described herein, in certain embodiments, is an altered human telomerasepolypeptide with at least 90% identity to the sequence set forth in SEQID NO: 1, wherein the altered human telomerase polypeptide comprises atleast one amino acid substitution that is at position R19, L22, R132,L152, D444, K492, E555, L556, T564, R572, R577, D637, L675, E727, R742,T765, R811, L840, G847, T874, L940, K981, V997, or P1020.

Described herein, in certain embodiments, is an altered human telomerasepolypeptide with at least 90% identity to the sequence set forth in SEQID NOs: 28 or 29, wherein the altered human telomerase polypeptide isnot identical to SEQ ID NO: 1.

Described herein, in certain embodiments, is a method for treating anindividual with cancer the method comprising administering to anindividual with cancer a polypeptide comprising at least one sequence ofSEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, or SEQID NO: 27.

Described herein, in certain embodiments, is a method for treating anindividual with cancer comprising administering to an individual withcancer an altered human telomerase polypeptide with at least 90%identity to the sequence set forth in SEQ ID NO: 1, wherein the alteredhuman telomerase polypeptide comprises at least one amino acidsubstitution that is at position R19, L22, R132, L152, D444, K492, E555,L556, T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847,T874, L940, K981, V997, or P1020.

Described herein, in certain embodiments, is a method for treating anindividual with cancer the method comprising administering to theindividual with cancer an altered human telomerase polypeptide at least90% identical to SEQ ID NO: 28 or 29, wherein the altered humantelomerase polypeptide is not identical to SEQ ID NO: 1.

Described herein, in certain embodiments, is a method of preparing acancer treatment the method comprising admixing a polypeptide comprisingat least one sequence of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ IDNO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10,SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15,SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20,SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25,SEQ ID NO: 26, or SEQ ID NO: 27, and a pharmaceutically acceptablevehicle, carrier, excipient, or combination thereof.

Described herein, in certain embodiments, is a method of preparing acancer treatment the method comprising admixing a composition comprisingan altered human telomerase polypeptide with at least 90% identity tothat set forth in SEQ ID NO: 1, comprising at least one amino acidsubstitution that is at position R19, L22, R132, L152, D444, K492, E555,L556, T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847,T874, L940, K981, V997, or P1020, and a pharmaceutically acceptablevehicle, carrier, excipient, or combination thereof.

Described herein, in certain embodiments, is a method of preparing acancer treatment the method comprising admixing an altered humantelomerase polypeptide at least 90% identical to SEQ ID NO: 28 or 29,wherein the altered human telomerase polypeptide is not identical to SEQID NO: 1 and a pharmaceutically acceptable vehicle, carrier, excipient,or combination thereof.

Certain Definitions

In the following description, certain specific details are set forth inorder to provide a thorough understanding of various embodiments.However, one skilled in the art will understand that the embodimentsprovided may be practiced without these details. Unless the contextrequires otherwise, throughout the specification and claims whichfollow, the word “comprise” and variations thereof, such as, “comprises”and “comprising” are to be construed in an open, inclusive sense, thatis, as “including, but not limited to.” As used in this specificationand the appended claims, the singular forms “a,” “an,” and “the” includeplural referents unless the content clearly dictates otherwise. Itshould also be noted that the term “or” is generally employed in itssense including “and/or” unless the content clearly dictates otherwise.Further, headings provided herein are for convenience only and do notinterpret the scope or meaning of the claimed embodiments.

As used herein the term “about ” refers to an amount that is near thestated amount by about 10%, 5%, or 1%.

As used herein “antigen ” refers to a molecule capable of inducing anadaptive immune response in the host organism.

As used herein “epitope” refers to the part of an antigen, protein, orpolypeptide that is recognized by the immune system, specifically byantibodies, B cell receptors, or T cell receptors.

As used herein “immunological adjuvant” refers to any substance that canbe administered with an antigen to increase the immune response inresponse to that antigen.

As used herein “T cell helper epitope” refers to a polypeptide capableof stimulating a CD4⁺ T cell to secrete immunostimulatory factors (e.g.,cytokines, chemokines) and improve the immunogenicity of antigens withregard to B cell, CD4⁺ T cell and/or cytotoxic CD8⁺ T cell responses.

Altered Telomerase Polypeptides

In certain embodiments, described herein, are compositions of matter.SEQ ID NO: 1 corresponds to the amino acid sequence of wild type humantelomerase protein. In certain embodiments, described herein, thecomposition is an altered telomerase polypeptide that has been alteredfrom the sequence set forth in SEQ ID NO: 1. In certain embodiments, thepolypeptide that has been altered from the sequence set forth in SEQ IDNO: 1, has been altered in a way to increase immunogenicity of one ormore T cell epitopes derived therefrom. In certain embodiments, thealtered telomerase polypeptide has been altered to correspond to theamino acid sequence set forth in SEQ ID NO: 28 or SEQ ID NO: 29. Incertain embodiments, the altered telomerase polypeptide has been alteredto possess 90% sequence identity to SEQ ID NO: 28 or SEQ ID NO: 29. Incertain embodiments, the altered telomerase polypeptide has been alteredto possess 95% sequence identity to SEQ ID NO: 28 or SEQ ID NO: 29. Incertain embodiments, the altered telomerase polypeptide has been alteredto possess 97% sequence identity to SEQ ID NO: 28 or SEQ ID NO: 29. Incertain embodiments, the altered telomerase polypeptide has been alteredto possess 98% sequence identity to SEQ ID NO: 28 or SEQ ID NO: 29. Incertain embodiments, the altered telomerase polypeptide has been alteredto possess 99% sequence identity to SEQ ID NO: 28 or SEQ ID NO: 29. Incertain embodiments, the altered telomerase polypeptide has been alteredto possess 100% sequence identity to SEQ ID NO: 28 or SEQ ID NO: 29. Incertain embodiments, SEQ ID NO: 28 or SEQ ID NO: 29 comprises one ormore T cell helper epitopes that have been inserted into the polypeptidesequence of SEQ ID NO: 28 or SEQ ID NO: 29, or at the N or C-terminalends, possibly joined by a flexible linker. In a further embodiment, thealtered telomerase polypeptide may comprise truncations or deletions ofamino acid residues that do not interfere with a T cell epitope.

In certain embodiments, described herein, are compositions of matter. Incertain embodiments, the composition of matter is an altered telomerasepolypeptide of SEQ ID NO: 1, wherein the alteration occurs at any one ormore of positions R19, L22, R132, L152, D444, K492, E555, L556, T564,R572, R577, D637, L675, E727, R742, T765, R811, L840, G847, T874, L940,K981, V997, P1020, or any combination thereof. In certain embodiments,the alteration of SEQ ID NO: 1 occurs at any two or more of positionsR19, L22, R132, L152, D444, K492, E555, L556, T564, R572, R577, D637,L675, E727, R742, T765, R811, L840, G847, T874, L940, K981, V997, orP1020. In certain embodiments, the alteration of SEQ ID NO: 1 occurs atany three or more of positions R19, L22, R132, L152, D444, K492, E555,L556, T564, R572, R577, D637, L675, E727, R742, T765, R811, L840, G847,T874, L940, K981, V997, or P1020. In certain embodiments, the alterationof SEQ ID NO: 1 occurs at any four or more of positions R19, L22, R132,L152, D444, K492, E555, L556, T564, R572, R577, D637, L675, E727, R742,T765, R811, L840, G847, T874, L940, K981, V997, or P1020. In certainembodiments, the alteration of SEQ ID NO: 1 occurs at any five or moreof positions R19, L22, R132, L152, D444, K492, E555, L556, T564, R572,R577, D637, L675, E727, R742, T765, R811, L840, G847, T874, L940, K981,V997, or P1020. In certain embodiments, the alteration of SEQ ID NO: 1occurs at any six or more of positions R19, L22, R132, L152, D444, K492,E555, L556, T564, R572, R577, D637, L675, E727, R742, T765, R811, L840,G847, T874, L940, K981, V997, or P1020. In certain embodiments, thealteration of SEQ ID NO: 1 occurs at any seven or more of positions R19,L22, R132, L152, D444, K492, E555, L556, T564, R572, R577, D637, L675,E727, R742, T765, R811, L840, G847, T874, L940, K981, V997, or P1020. Incertain embodiments, the alteration of SEQ ID NO: 1 occurs at any eightor more of positions R19, L22, R132, L152, D444, K492, E555, L556, T564,R572, R577, D637, L675, E727, R742, T765, R811, L840, G847, T874, L940,K981, V997, or P1020. In certain embodiments, the alteration of SEQ IDNO: 1 occurs at any nine or more of positions R19, L22, R132, L152,D444, K492, E555, L556, T564, R572, R577, D637, L675, E727, R742, T765,R811, L840, G847, T874, L940, K981, V997, or P1020. In certainembodiments, the alteration of SEQ ID NO: 1 occurs at any ten or more ofpositions R19, L22, R132, L152, D444, K492, E555, L556, T564, R572,R577, D637, L675, E727, R742, T765, R811, L840, G847, T874, L940, K981,V997, or P1020. In certain embodiments, the alteration of SEQ ID NO: 1occurs at any fifteen or more of positions R19, L22, R132, L152, D444,K492, E555, L556, T564, R572, R577, D637, L675, E727, R742, T765, R811,L840, G847, T874, L940, K981, V997, or P1020. In certain embodiments,the alteration of SEQ ID NO: 1 occurs at any twenty or more of positionsR19, L22, R132, L152, D444, K492, E555, L556, T564, R572, R577, D637,L675, E727, R742, T765, R811, L840, G847, T874, L940, K981, V997, orP1020. In certain embodiments, the alteration of SEQ ID NO: 1 occurs atany twenty-five or more of positions R19, L22, R132, L152, D444, K492,E555, L556, T564, R572, R577, D637, L675, E727, R742, T765, R811, L840,G847, T874, L940, K981, V997, or P1020. In certain embodiments, thealtered telomerase polypeptide retains 90% sequence identity to SEQ IDNO: 1. In certain embodiments, the altered telomerase polypeptideretains 95% sequence identity to SEQ ID NO: 1. In certain embodiments,the altered telomerase polypeptide retains 97% sequence identity to SEQID NO: 1. In certain embodiments, the altered telomerase polypeptideretains 98% sequence identity to SEQ ID NO: 1. In certain embodiments,the altered telomerase polypeptide retains 99% sequence identity to SEQID NO: 1. In certain embodiments, the altered telomerase polypeptidecomprises a T cell helper epitope that has been inserted into thepolypeptide sequence. In certain embodiments, the T cell helper epitopeis inserted at the N-terminus. In certain embodiments, the T helperepitope is inserted at the C-terminus. In certain embodiments, the Tcell helper epitope is inserted in any region of the altered telomerasepolypeptide that does not disrupt any T cell epitope listed as SEQ IDNO: 2 to SEQ ID NO: 27. In certain embodiments, the T cell helperepitope is inserted in the altered telomerase polypeptide somewherebetween amino acids 140 and 440. In certain embodiments, the T cellhelper epitope is inserted in the altered telomerase polypeptidesomewhere between amino acids 500 and 550. In certain embodiments, the Tcell helper epitope is inserted in the altered telomerase polypeptidesomewhere between amino acids 770 and 810. In certain embodiments, the Tcell helper epitope comprises a non-human polypeptide derived from avirus, bacteria, or parasite. In certain embodiments, the T cell helperepitope comprises a sequence from the tetanus toxoid protein. In certainembodiments, the T cell helper epitope is set forth SEQ ID NO: 30. Incertain embodiments, the composition comprises a T cell helper epitopethat is a separate polypeptide from the altered telomerase polypeptide.In a further embodiment, the altered telomerase polypeptide may comprisetruncations or deletions of amino acid residues that do not interferewith a T cell epitope.

HLA Binding Properties of Altered Telomerase Peptides

In certain embodiments, amino acid alterations in SEQ ID NO: 1 producepolypeptides that increase binding affinity to an HLA molecule. Incertain embodiments, an alteration increases binding of an alteredpeptide to an HLA molecule by two-fold. In certain embodiments, analteration increases binding of an altered peptide to an HLA molecule byfive-fold. In certain embodiments, an alteration increases binding of analtered peptide to an HLA molecule by ten-fold. In certain embodiments,the HLA molecule is any one or more of types A1, A2, A3, A11, A24, B7and B44.

In certain embodiments, described herein, are compositions of matter. Incertain embodiments, the composition of matter is a polypeptide. Incertain embodiments, the polypeptide comprises any one or more aminoacid sequence as set forth in SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ IDNO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ IDNO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ IDNO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ IDNO: 25, SEQ ID NO: 26, SEQ ID NO: 27 (also referred to as SEQ ID NO:2 toSEQ ID NO: 27 for brevity), or any combination thereof. Table 1 showsSEQ ID NO:2 to SEQ ID NO: 27 and the HLA type bound by each. In certainembodiments, the polypeptide comprises any two or more amino acidsequence as set forth in SEQ ID NO:2 to SEQ ID NO: 27. In certainembodiments, the polypeptide comprises any three or more amino acidsequence as set forth in SEQ ID NO:2 to SEQ ID NO: 27. In certainembodiments, the polypeptide comprises any four or more amino acidsequence as set forth in SEQ ID NO:2 to SEQ ID NO: 27. In certainembodiments, the polypeptide comprises any five or more amino acidsequence as set forth in SEQ ID NO:2 to SEQ ID NO: 27. In certainembodiments, the polypeptide comprises any six or more amino acidsequence as set forth in SEQ ID NO:2 to SEQ ID NO: 27. In certainembodiments, the polypeptide comprises any seven or more amino acidsequence as set forth in SEQ ID NO:2 to SEQ ID NO: 27. In certainembodiments, the polypeptide comprises any eight or more amino acidsequence as set forth in SEQ ID NO:2 to SEQ ID NO: 27. In certainembodiments, the polypeptide comprises any nine or more amino acidsequence as set forth in SEQ ID NO:2 to SEQ ID NO: 27. In certainembodiments, the polypeptide comprises any ten or more amino acidsequence as set forth in SEQ ID NO:2 to SEQ ID NO: 27. In certainembodiments, the polypeptide comprises any fifteen or more amino acidsequence as set forth in SEQ ID NO:2 to SEQ ID NO: 27. In certainembodiments, the polypeptide comprises any twenty or more amino acidsequence as set forth in SEQ ID NO:2 to SEQ ID NO: 27. In certainembodiments, the polypeptide comprises any twenty-five or more aminoacid sequence as set forth in SEQ ID NO:2 to SEQ ID NO: 27. In certainembodiments, the polypeptide does not comprise SEQ ID NO: 12. In certainembodiments, the polypeptide does not comprise SEQ ID NO: 13.

In certain embodiments, the poly peptide comprises any two or moresequences set forth in SEQ ID NO:2 to SEQ ID NO: 27, further comprisingamino acid linkers in between each polypeptide set forth in SEQ ID NO:2to SEQ ID NO: 27. In certain embodiments, the linker sequence isengineered to promote proper cleave by the cell during processing of thepolypeptide. In certain embodiments, the linker is at least five aminoacids in length. In certain embodiments, the linker is at least sevenamino acids in length. In certain embodiments, the linker is at leastten amino acids in length. In certain embodiments, the polypeptide is atleast 20 amino acids in length. In certain embodiments, the polypeptideis at least 30 amino acids in length. In certain embodiments, thepolypeptide is at least 40 amino acids in length. In certainembodiments, the polypeptide is at least 50 amino acids in length. Incertain embodiments, the polypeptide is at least 100 amino acids inlength. In certain embodiments, the polypeptide is at least 150 aminoacids in length. In certain embodiments, the polypeptide is at least 200amino acids in length. In certain embodiments, the polypeptide is lessthan 500 amino acids in length. In certain embodiments, the polypeptideis less than 400 amino acids in length. In certain embodiments, thepolypeptide is less than 300 amino acids in length.

In certain embodiments, the polypeptide comprises at least one aminoacid sequence set forth in SEQ ID NO:2 to SEQ ID NO: 27, and a T cellhelper epitope. In certain embodiments, the T cell helper epitope isinserted at the N-terminus. In certain embodiments, the T helper epitopeis inserted at the C-terminus. In certain embodiments, the T cell helperepitope is inserted in any region of the polypeptide that does notdisrupt another T cell epitope set forth in SEQ ID NO: 2 to SEQ ID NO:27. In certain embodiments, the T cell helper epitope comprises anon-human polypeptide derived from a virus, bacteria, or parasite. Incertain embodiments, the T cell helper epitope is set forth in SEQ IDNO: 30 to SEQ ID NO: 55. In certain embodiments, the T cell helperepitope comprises a sequence from the tetanus toxoid protein. In certainembodiments, the T cell helper epitope is set forth in SEQ ID NO: 30. Incertain embodiments, the composition comprises a T cell helper epitopethat is separate polypeptide from the altered telomerase polypeptide.

In certain embodiments, the polypeptide comprises all polypeptides knownto bind a given HLA type. In certain embodiments, the polypeptidecomprises A1 binders SEQ ID NO: 19 and SEQ ID NO: 21. In certainembodiments, the polypeptide comprises A2 binders SEQ ID NO: 5, SEQ IDNO: 6, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 16, SEQ ID NO: 20, andSEQ ID NO: 25. In certain embodiments, the polypeptide comprises A3binders SEQ ID NO: 8, SEQ ID NO: 11, SEQ ID NO: 26, and SEQ ID NO: 27.In certain embodiments, the polypeptide comprises A11 binders SEQ ID NO:8, SEQ ID NO: 17, and SEQ ID NO: 18. In certain embodiments, thepolypeptide comprises A24 binders SEQ ID NO: 14, SEQ ID NO: 15, and SEQID NO: 24. In certain embodiments, the polypeptide comprises B7 bindersSEQ ID NO: 4, SEQ ID NO: 7, and SEQ ID NO: 23. In certain embodiments,the polypeptide comprises B44 binders SEQ ID NO: 2, SEQ ID NO: 9, andSEQ ID NO: 24.

In certain embodiments, the polypeptide comprises at least sevendifferent sequences, wherein each of the seven different sequences bindsa different human leukocyte antigen selected from the group consistingof A1, A2, A3, A11, A24, B3, B7 and B44. In certain embodiments, thepolypeptide comprises one A1 binder selected from the group consistingof SEQ ID NO: 19 and SEQ ID NO: 21; one A2 binder selected from thegroup consisting of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 10, SEQ IDNO: 12, SEQ ID NO: 16, SEQ ID NO: 20, and SEQ ID NO: 25; one A3 binderselected from the group consisting of SEQ ID NO: 8, SEQ ID NO: 11, SEQID NO: 26, and SEQ ID NO: 27; one A11 binder selected from the groupconsisting of SEQ ID NO: 8, SEQ ID NO: 17, and SEQ ID NO: 18; one A24binder selected from the group consisting of SEQ ID NO: 14, SEQ ID NO:15, and SEQ ID NO: 24; one B7 binder selected from the group consistingof SEQ ID NO: 4, SEQ ID NO: 7, and SEQ ID NO: 23; and one B44 binderselected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 9, andSEQ ID NO: 24

TABLE 1 SEQ HLA TYPE SEQ HLA TYPE ID SEQUENCE BOUND ID SEQUENCE BOUND 2A EVLPLATF B44 15 Y YVVGARTF A24 3 A EV R PLATF B44 16 Y LGASVLGL A2 4 RPLATFVRRL B7 17 LT M VIASIIK A11 5 AL M GSGAWGL A2 18 CV M RYAVVQK A11 6Y LARCALFV A2 19 VS D LTDLQPY A1 7 R PRRLVQLL B7 20 FL M FMCHHAV A2 8 NTM KFISLGK A11 and A3 21 ST D LCSLCY A1 9 VE M LRSFFY B44 22 CY M DMENKLFA24 10 Y LLRSFFYV A2 23 R PHLTHAKTF B7 11 YV Y ETTFQK A3 24 A EVQSDYSSYB44 12 Y LFFY M KSV A2 25 RL M CHSLFL A2 13 Y LFFYRKSV A2 26 QT Y CTNIYKA3 14 FY M KSVWSKL A24 27 QL Y FHQQVWK A3 Bold and underline denotesresidue altered from wild type human telomerase sequence

Nucleic Acids

In certain embodiments, described herein, are nucleic acids that encodethe polypeptides and altered telomerase polypeptides described herein.In certain embodiments, the nucleic acid is a plasmid. In certainembodiments, the nucleic acid is a viral vector. In certain embodiments,the viral vector is an adenovirus, lentivirus, retrovirus, adenoassociated virus, or vaccinia virus. In certain embodiments, the nucleicacid comprises RNA. In certain embodiments, the nucleic acid encodes anyof SEQ ID NOs: 2 to 55. In certain embodiments, the nucleic acid encodesany polypeptide embodiment described herein. In certain embodiments, thenucleic acid is expressed via a universal promoter such as the CMVpromoter. In certain embodiments, the nucleic acid is expressed via atissue specific promoter. In certain embodiments, the tissue specificpromoter is a B cell specific promoter. In certain embodiments, thetissue specific promoter is the immunoglobulin promoter/enhancer.

T Cell Helper Epitope

In certain embodiments, any of the compositions described herein,comprise a T cell helper epitope. In certain embodiments, any of thepolypeptides described herein, comprise a T cell helper epitope. Incertain embodiments, any of the treatment methods described herein,comprise administering an altered telomerase polypeptide in conjunctionwith a T cell helper epitope. In certain embodiments, the T cell helperepitope is a promiscuous binder and binds more than one human MHC ClassII HLA type. In certain embodiments, the T cell helper epitope comprisesa non-human polypeptide derived from a virus, bacteria, or parasite. Incertain embodiments, the T cell helper epitope comprises an artificialsequence. In certain embodiments, the T cell helper epitope comprises achimeric sequence from a plurality of antigens. In certain embodiments,the T cell helper epitope comprises any of the SEQ IDs listed in Table2. In certain embodiments, the T cell helper epitope comprises any ofSEQ ID NO:30 to SEQ ID NO: 55. In certain embodiments, the T cell helperepitope comprises a sequence from the tetanus toxoid protein. In certainembodiments, the T cell helper epitope is set forth in SEQ ID NO: 30. Incertain embodiments, the T cell helper epitope is inserted intotelomerase in such a way a to destroy the telomerase activity.

TABLE 2 SEQ ID SEQUENCE SOURCE 30 QYIKANSKFIGITE Tetanus Toxoid 31AKFVAAWTLKAAA Artificial 32 EKKIAKMEKASSVFNVVNS Malaria 33IEKKIAKMEKASSVFNVVNS Malaria 34 DIEKKIAKMEKASSVFNVVNS Malaria 35DIEKKIAKMEKASSVFNVVN Malaria 36 DIEKKIAKMEKASSVFNVV Malaria 37DIEKKIAKMEKASSVFNV Malaria 38 ILMQYIKANSKFIGI Chimeric- tetanus toxoid;diphtheria toxoid 39 QSIALSSLMVAQAIP Chimeric- tetanus toxoid;diphtheria toxoid 40 ILMQYIKANSKFIGIPMGLPQ Chimeric- tetanus toxoid;SIALSSLMVAQ diphtheria toxoid 41 ILMQYIKANSKFIGIKVSRQSChimeric- tetanus toxoid; IALSSLMVAQ diphtheria toxoid 42KVLVLNPSVAATLGF Hepatitis C virus 43 PTHFKYHEKHYYNAQ BK Virus 44LFVVYRDSIPHAACH Human papilloma virus 45 GLYNLLIRCLRCQKPHuman papilloma virus 46 GKTVWFVPSIKAGND Dengue virus 47 MYFHRRDLRLASNAIDengue virus 48 VERLKRMAISGDDCVVK Dengue virus 49 ANAIFKLTYQNKVVKVQDengue virus 50 ASIAARGYISTRVGM Dengue virus 51 DENPYKTWAYHGSYEVKDengue virus 52 EAAAIFMTATPPGTA Dengue virus 53 MVTQMAMTDTTPFGQQRDengue virus 54 KKRNLTIMDLHPGSG Dengue virus 55 LSEJKGVIVHRLEGVMeasles virus

Antigen Presenting Cells

In certain embodiments, described herein, telomerase polypeptides, forma complex with HLA molecules on the surface of antigen presenting cells.In certain embodiments, the polypeptide comprises a SEQ ID set forth inSEQ ID NOs:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ IDNO: 27, or any combination thereof. In certain embodiments, describedherein, 8-10 contiguous amino acids derived from an altered telomerasepolypeptide by cellular processing, form a complex with one or more HLAmolecules on the surface of antigen presenting cell. In certainembodiments, the antigen presenting cell encounters the telomerasepolypeptide in vivo after the polypeptide has been administered to anindividual. In certain embodiments, the polypeptide is added to antigenpresenting cells ex vivo. In certain embodiments, the antigen presentingcell has been treated ex vivo to activate its antigen presentingcapacity. In certain embodiments, the antigen presenting cell has beentreated with interferon gamma, granulocyte-macrophage colony-stimulatingfactor (GM-CSF), colony-stimulating factor, a TLR ligand,lipopolysaccharide, CpG oligonucleotide, or any combination thereof. Incertain embodiments, the antigen presenting cell comprises a B cell. Incertain embodiments, the antigen presenting cell comprises a dendriticcell. In certain embodiments, the antigen presenting cell comprises amacrophage. In certain embodiments, the antigen presenting cellcomprises an artificial antigen presenting cell.

Immunological Adjuvants

In certain embodiments, described herein, are compositions of matterthat comprise an altered telomerase polypeptide and an immunologicaladjuvant. In certain embodiments, described herein, are compositions ofmatter that comprise any of SEQ ID NOs: 2 to 29 and an immunologicaladjuvant. In certain embodiments, the adjuvant comprises an adjuvantcurrently used in vaccination. In certain embodiments, the adjuvant ismineral salt. In certain embodiments, the adjuvant comprises alum salt.In certain embodiments, the adjuvant comprises aluminum phosphate oraluminum hydroxide. In certain embodiments, the adjuvant comprises QuilA or saponin QS-21. In certain embodiments, the adjuvant comprisesN-acetyl muramyl-L-alanyl-D-isoglutamine, also called MDP. In certainembodiments, the adjuvant comprises IFA, Montanide, Adjuvant 65, andLipovant. In certain embodiments, the adjuvant comprises a cytokine suchas interferon gamma or GM-CSF.

Toll-Like Receptor Ligands

In certain embodiments, described herein, are compositions of matterthat comprise an altered telomerase polypeptide and a Toll-like receptor(TLR) ligand, a STING agonist, or RIG-I agonist. In certain embodiments,described herein, are compositions of matter that comprise any of SEQ IDNOs: 2 to 29 and a TLR ligand. In certain embodiments, the TLR ligand isLPS or a CpG oligonucleotide. In certain embodiments, the TLR ligandactivates signaling through any one of TLR2, TLR3, TLR4, TLR5, TLR6,TLR7, TLR8, or TLR9. In certain embodiments, the STING agonist comprisesa cyclic dinucleotide. In certain embodiments, the RIG-1 agonistcomprises a 5′ppp-dsRNA.

Pharmaceutically Acceptable Vehicles, Carrier and Excipients

In certain embodiments, described herein, are compositions of matterthat comprise an altered telomerase polypeptide and a pharmaceuticallyacceptable vehicle, carrier, or excipient. In certain embodiments,described herein, are compositions of matter that comprise any of SEQ IDNOs: 2 to 29 and a pharmaceutically acceptable vehicle, carrier orexcipient. In certain embodiments, the pharmaceutically acceptablevehicle, carrier, or excipient comprises a pH buffer or pH modifier. Incertain embodiments, the pH buffer or pH modifier comprises sodiumbicarbonate, HEPES, MOPS, MEPES, phosphate buffer, succinate buffer,citric acid, ascorbic acid, or any combination thereof. In certainembodiments, the pharmaceutically acceptable vehicle, carrier orexcipient comprises a salt solution. In certain embodiments, the saltsolution comprises sodium chloride, potassium chloride, calciumchloride, hemin chloride, benzethonium chloride, or any combinationthereof. In certain embodiments, the pharmaceutically acceptablevehicle, carrier or excipient comprises a carbohydrate. In certainembodiments, the carbohydrate comprises sucrose, dextrose, trehalose,lactose, cellulose, sorbitol, galactose, dextran, xanthan, or anycombination thereof. In certain embodiments, the pharmaceuticallyacceptable vehicle, carrier or excipient comprises an amino acid orprotein. In certain embodiments, the amino acid or protein comprisesgelatin, egg protein, yeast extract, glutamate, albumin. In certainembodiments, the pharmaceutically acceptable vehicle, carrier orexcipient comprises an emulsifier. In certain embodiments, theemulsifier comprises octylphenol ethoxylate (Triton X-100), polysorbate20, polysorbate 80 (Tween 80), sodium deoxy cholate, or any combinationthereof. In certain embodiments, the pharmaceutically acceptablevehicle, carrier or excipient comprises a chelator. In certainembodiments, the chelator comprises ethylene diamine tetra acetic acidsodium (EDTA), EGTA, or any combination thereof. In certain embodiments,the pharmaceutically acceptable vehicle, carrier or excipient comprisesa liposome. In certain embodiments, the liposome comprises aphospholipid, such as, for example, phosphatidylcholine. The liposomecan be multilamellar or unilamellar.

Routes of Administration

In certain embodiments, the polypeptides and nucleic acids of thecurrent disclosure can be administered in a variety of ways. In certainembodiments, the polypeptides are delivered via a subcutaneous orintradermal injection. In certain embodiments, the polypeptides can beadministered by electroporation. In certain embodiments, thepolypeptides are delivered via an intra-tumor injection. In certainembodiments, the polypeptides are delivered via injection to the spleenor lymph nodes. In certain embodiments, the polypeptides are deliveredbound to the HLA of an antigen presenting cell by intravenousadministration. In certain embodiments, the antigen presenting cell is aB cell. In certain embodiments, the antigen presenting cell is adendritic cell. In certain embodiments, the nucleic acids of the currentdisclosure can be administered by transfection. In certain embodiments,the nucleic acids of the current disclosure can be administered byelectroporation. In certain embodiments, the nucleic acids of thecurrent disclosure can be administered by transfection of an antigenpresenting cell ex vivo. In certain embodiments, the antigen presentingcell is a B cell. In certain embodiments, the antigen presenting cell isa dendritic cell. In certain embodiments, the altered telomerasepolypeptides can be used in conjunction with chimeric antigen receptor(CAR) T cells or NK cells. In certain embodiments, the CAR-T cells arespecific for a telomerase peptide set forth is SE ID NO:2 to SEQ ID NO:27. In certain embodiments, the CAR-NK cells are specific for atelomerase peptide set forth is SE ID NO:2 to SEQ ID NO: 27.

In certain embodiments, antigen presenting cells are isolated from anindividual with cancer, the antigen presenting cell is transfected exvivo with a nucleic acid encoding any of the altered telomerasepolypeptides of the present disclosure, and then administered to theindividual. In certain embodiments, the antigen presenting cell istransfected by a lipid transfection reagent. In certain embodiments, theantigen presenting cell is transfected by electroporation. In certainembodiments, the antigen presenting cell is transfected by a viralvector. In certain embodiments, the antigen presenting cell istransfected spontaneously without the aid of a specific transfectionreagent. In certain embodiments, the antigen presenting cell comprises aB cell. In certain embodiments, the antigen presenting cell comprises adendritic cell. In certain embodiments, the antigen presenting cellcomprises a macrophage. In certain embodiments, b 1×10 ⁵ to 5×10⁶ of thetransfected antigen presenting cells are administered to an individual.In certain embodiments, at least 1×10⁵ of the transfected antigenpresenting cells are administered to an individual. In certainembodiments, at least 1×10⁶ of the transfected antigen presenting cellsare administered to an individual.

Schedules and Method of Administration

In certain embodiments, described herein, are methods of treating cancerusing the polypeptides or nucleotides of the present disclosure. Incertain embodiments, any of the polypeptides or nucleotides areadministered once to an individual in need. In certain embodiments, anyof the polypeptides or nucleotides are administered twice to anindividual in need. In certain embodiments, any of the polypeptides ornucleotides are administered three times to an individual in need. Incertain embodiments, any of the polypeptides or nucleotides areadministered four times or more to an individual in need. In certainembodiments, individuals are primed with one polypeptide and boostedwith the same polypeptide. In certain embodiments, individuals areprimed with one polypeptide and boosted with a different polypeptide. Incertain embodiments, individuals are primed with a nucleic acid andboosted with a polypeptide. In certain embodiments, doses are given oncea week, once every two weeks, once a month, or once a year. In certainembodiments, the interval between doses is at least one month. Incertain embodiments, the interval between doses is at least two months.In certain embodiments, individuals who have responded to the treatmentare given annual or semi-annual booster doses.

Method of Preparation of a Cancer Treatment

In certain embodiments, described herein, are methods of producingpolypeptides comprising SEQ ID NO:2 to SEQ ID NO: 27, and alteredtelomerase polypeptides. In certain embodiments, are methods thatcomprise preparing any of SEQ ID NOs: 2 to 55. The polypeptides of thisdisclosure can be produced by techniques know in the art. In certainembodiments, the polypeptides are synthesized. In certain embodiments,the polypeptides are expressed in a suitable expression system andpurified using standard techniques such as filtration, precipitation,chromatography, centrifugation, or any combination thereof.

Cancers

In certain embodiments, the compositions and methods described herein,are for use in treating an individual with cancer. In certainembodiments, the individual has any stage of histologically confirmedcancer. In certain embodiments, the individual is at risk of developingcancer. In certain embodiments, the cancer is telomerase positive. Incertain embodiments, the cancer is any cancer that has been shown tohave telomerase activity or elevated levels of telomerase. Elevatedlevels of telomerase activity can be shown by TRAP assay, or elevationsin telomerase mRNA or protein levels. In certain embodiments, the canceris caused by a mutation in the telomerase promoter region. In certainembodiments, the cancer is associated with a mutation in the telomerasepromoter region. In certain embodiments, the cancer is a solid tumor. Incertain embodiments, the cancer is hematological. In certainembodiments, the cancer is a brain cancer. In certain embodiments, thebrain cancer is a glioblastoma. In certain embodiments, the cancer is aliver cancer. In certain embodiments, the liver cancer is hepatocellularcarcinoma. In certain embodiments, the cancer is of the urogenitalsystem. In certain embodiments, the urogenital system cancer is bladdercancer. In certain embodiments, the urogenital system cancer is prostatecancer. In certain embodiments, the cancer is kidney cancer. In certainembodiments, the cancer is thyroid cancer. In certain embodiments, thecancer is prostate cancer, breast cancer, colon cancer, pancreaticcancer, melanoma, lung cancer, stomach cancer, or brain cancer. Incertain embodiments, the cancer is a blood cancer such as a leukemia ormyeloma. In certain embodiments, the blood cancer is chronic myelogenousleukemia, acute myelogenous leukemia, chronic lymphocytic leukemia,acute lymphocytic leukemia, or multiple myeloma.

EXAMPLES

The following examples are meant to be illustrative and do not serve tolimit the invention described herein.

Example 1 A Clinical Trial for Bladder Cancer Using B Cells transfectedwith Plasmid Expressing an Altered Telomerase Polypeptide

A clinical trial will be conducted for patients with a telomerasespecific cancer such as bladder/urothelial cancer. The primary efficacyendpoint will be the percentage survivorship 24 months post treatment.The treatment will be with a B cell population transfected with anucleic acid plasmid encoding an altered telomerase corresponding to SEQID NO: 28 or 29. Peripheral blood mononuclear cells will be isolatedfrom each patient, spontaneously transfected ex vivo with plasmid DNA,and cultured for 24 hours under cell type appropriate cultureconditions. After this culture period patients will be injectedintravenously with 1×10⁵ to 5×10⁶ of their own B cells in an autologoustransfer. Patients will be administered a total of three treatments 1month apart.

Example 2 Immunization of Patients with Melanoma Using an AlteredTelomerase Polypeptide

One mg of an altered telomerase polypeptide will be administeredsubcutaneously or intradermally to patients with melanoma. The alteredtelomerase polypeptide will be prepared with an immunological adjuvant.Patients will be administered a total of three treatments one monthapart.

Example 3 Immunization of Patients with Hepatocellular Carcinoma UsingPlasmid DNA in Conjunction with Electroporation

100 micrograms of a plasmid encoding an altered telomerase peptide willbe administered intradermally at ten different sites on the patientusing electroporation. A total of one milligram will be administered.

Example 4 Delivering a Booster Dose Via a Viral Vector

A booster dosage of a viral vector will be administered to a personpreviously immunized with nucleic acid or peptide. The viral vector willencode a polypeptide corresponding to SEQ ID NO: 28 or SEQ ID NO: 29 orany other polypeptide disclosed herein. The booster will occur at leastone month after the initial immunization.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein may be employed in practicing the invention.

SEQ ID NO: 1 Wild type human telomerase        10         20          30         40         50MPRAPRCRAV RSLLRSHYRE  VLPLATFVRR LGPQGWRLVQ RGDPAAFRAL        60         70          80         90        100VAQCLVCVPW DARPPPAAPS  FRQVSCLKEL VARVLQRLCE RGAKNVLAFG       110        120         130        140        150FALLDGARGG PPEAFTTSVR  SYLPNTVTDA LRGSGAWGLL LRRVGDDVLV       160        170         180        190        200HLLARCALFV LVAPSCAYQV  CGPPLYQLGA ATQARPPPHA SGPRRRLGCE       210        220         230        240        250RAWNHSVREA GVPLGLPAPG  ARRRGGSASR SLPLPKRPRR GAAPEPERTP       260        270         280        290        350VGQGSWAHPG RTRGPSDRGF  CVVSPARPAE EATSLEGALS GTRHSHPSVG       310        320         330        340        350RQHHAGPPST SRPPRPWDTP  CPPVYAETKH FLYSSGDKEQ LRPSFLLSSL       360        370         380        390        400RPSLTGARRL VETIFLGSRP  WMPGTPRRLP RLPQRYWQMR PLFLELLGNH       410        420         430        440        450AQCPYGVLLK THCPLRAAVT  PAAGVCAREK PQGSVAAPEE EDTDPRRLVQ       460        470         480        490        500LLRQHSSPWQ VYGFVRACLR  RLVPPGLWGS RHNERRFLRN TKKFISLGKH       510        520         530        540        550AKLSLQELTW KMSVRDCAWL  RRSPGVGCVP AAEHRLREEI LAKFLHWLMS       560        570         580        590        600VYVVELLRSF FYVTETTFQK  NRLFFYRKSV WSKLQSIGIR QHLKRVQLRE       610        620         630        640        650LSEAEVRQHR EARPALLTSR  LRFIPKPDGL RPIVNMDYVV GARTFRREKR       660        670         680        690        700AERLTSRVKA LFSVLNYERA  RRPGLLGASV LGLDDIHRAW RTFVLRVRAQ       710        720         730        740        750DPPPELYFVK VDVTGAYDTI  PQDRLTEVIA SIIKPQNTYC VRRYAVVQKA       760        770         780        790        800AHGHVRKAFK SHVSTLTDLQ  PYMRQFVAHL QETSPLRDAV VIEQSSSLNE       810        820         830        840        850ASSGLFDVFL RFMCHHAVRI  RGKSYVQCQG IPQGSILSTL LCSLCYGDME       860        870         880        890        900NKLFAGIRRD GLLLRLVDDF  LLVTPHLTHA KTFLRTLVRG VPEYGCVVNL       910        920         930        940        950RKTVVNFPVE DEALGGTAFV  QMPAHGLFPW CGLLLDTRTL EVQSDYSSYA       960        970         980        990       1000RTSIRASLTF NRGFKAGRNM  RRKLFGVLRL KCHSLFLDLQ VNSLQTVCTN      1010       1020        1030       1040       1050IYKILLLQAY RFHACVLQLP  FHQQVWKNPT FFLRVISDTA SLCYSILKAK      1060       1070        1080       1090       1100NAGMSLGAKG AAGPLPSEAV  QWLCHQAFLL KLTRHRVTYV PLLGSLRTAQ      1110        112        1130 TQLSRKLPGT TLTALEAAAN  PALPSDFKTI LDSEQ ID NO: 28 Altered human telomemse variant 1        10         20          30         40         50MPRAPRCRAV RSLLRSHYAE  VRPLATFVRR LGPQGWRLVQ RGDPAAFRAL        60         70          80         90        100VAQCLVCVPW DARPPPAAPS  FRQVSCLKEL VARVLQRLCE RGAKNVLAFG       110        120         130        140        150FALLDGARGG PPEAFTTSVR  SYLPNTVTDA LMGSGAWGLL LRRVGDDVLV       160        170         180        190        200HLLARCALFV LVAPSCAYQV  CGPPLYQLGA ATQARPPPHA SGPRRRLGCE       210        220         230        240        250RAWNHSVREA GVPLGLPAPG  ARRRGGSASR SLPLPKRPRR GAAPEPERTP       260        270         280        290        350VGQGSWAHPG RTRGPSDRGF  CVVSPARPAE EATSLEGALS GTRHSHPSVG       310        320         330        340        350RQHHAGPPST SRPPRPWDTP  CPPVYAETKH FLYSSGDKEQ LRPSFLLSSL       360        370         380        390        400RPSLTGARRL VETIFLGSRP  WMPGTPRRLP RLPQRYWQMR PLFLELLGNH       410        420         430        440        450AQCPYGVLLK THCPLRAAVT  PAAGVCAREK PQGSVAAPEE EDTRPRRLVQ       460        470         480        490        500LLRQHSSPWQ VYGFVRACLR  RLVPPGLWGS RHNERRFLRN TMKFISLGKH       510        520         530        540        550AKLSLQELTW KMSVRDCAWL  RRSPGVGCVP AAEHRLREEI LAKFLHWLMS       560        570         580        590        600VYVVEMLRSF FYVYETTFQK  NYLFFYMKSV WSKLQSIGIR QHLKRVQLRE       610        620         630        640        650LSEAEVRQHR EARPALLTSR  LRFIPKPDGL RPIVNMYYVV GARTFRREKR       660        670         680        690        700AERLTSRVKA LFSVLNYERA  RRPGYLGASV LGLDDIHRAW RTFVLRVRAQ       710        720         730        740        750DPPPELYFVK VDVTGAYDTI  PQDRLTMVIA SIIKPQNTYC VMRYAVVQKA       760        770         780        790        800AHGHVRKAFK SHVSDLTDLQ  PYMRQFVAHL QETSPLRDAV VIEQSSSLNE       810        820         830        840        850ASSGLFDVFL MFMCHHAVRI  RGKSYVQCQG IPQGSILSTD LCSLCYMDME       860        870         880        890        900NKLFAGIRRD GLLLRLQYIK ANSKEFIGITE LFLLVRPHLT HAKTFLRTLV       910        920         930        940        950RGVPEYGCVV NLRKTVVNFP  VEDEALGGTA FVQMPAHGLF PWCGLLLDTR       960        970         980        990       1000TAEVQSDYSS YARTSIRASL  TFNRGFKAGR NMRRKLFGVL RLMCHSLFLD      1010       1020        1030       1040       1050LQVNSLQTYC TNIYKILLLQ  AYRFHACVLQ LYFHQQVWKN PTFFLRVISD      1060       1070        1080       1090       1100TASLCYSILK AKNAGMSLGA  KGAAGPLPSE AVQWLCHQAF LLKLTRHRVT      1110        112        1130       1140YVPLLGSLRT AQTQLSRKLP  GTTLTALEAA ANPALPSDFK TILD SEQ ID NO: 29Altered human telomemse variant 2        10         20          30         40         50MPRAPRCRAV RSLLRSHYAE  VRPLATFVRR LGPQGWRLVQ RGDPAAFRAL        60         70          80         90        100VAQCLVCVPW DARPPPAAPS  FRQVSCLKEL VARVLQRLCE RGAKNVLAFG       110        120         130        140        150FALLDGARGG PPEAFTTSVR  SYLPNTVTDA LMGSGAWGLL LRRVGDDVLV       160        170         180        190        200HLLARCALFV LVAPSCAYQV  CGPPLYQLGA ATQARPPPHA SGPRRRLGCE       210        220         230        240        250RAWNHSVREA GVPLGLPAPG  ARRRGGSASR SLPLPKRPRR GAAPEPERTP       260        270         280        290        350VGQGSWAHPG RTRGPSDRGF  CVVSPARPAE EATSLEGALS GTRHSHPSVG       310        320         330        340        350RQHHAGPPST SRPPRPWDTP  CPPVYAETKH FLYSSGDKEQ LRPSFLLSSL       360        370         380        390        400RPSLTGARRL VETIFLGSRP  WMPGTPRRLP RLPQRYWQMR PLFLELLGNH       410        420         430        440        450AQCPYGVLLK THCPLRAAVT  PAAGVCAREK PQGSVAAPEE EDTRPRRLVQ       460        470         480        490        500LLRQHSSPWQ VYGFVRACLR  RLVPPGLWGS RHNERRFLRN TMKFISLGKH       510        520         530        540        550AKLSLQELTW KMSVRDCAWL  RRSPGVGCVP AAEHRLREEI LAKFLHWLMS       560        570         580        590        600VYVVYLLRSF FYVYETTFQK  NYLFFYMKSV WSKLQSIGIR QHLKRVQLRE       610        620         630        640        650LSEAEVRQHR EARPALLTSR  LRFIPKPDGL RPIVNMYYVV GARTFRREKR       660        670         680        690        700AERLTSRVKA LFSVLNYERA  RRPGYLGASV LGLDDIHRAW RTFVLRVRAQ       710        720         730        740        750DPPPELYFVK VDVTGAYDTI  PQDRLTMVIA SIIKPQNTYC VMRYAVVQKA       760        770         780        790        800AHGHVRKAFK SHVSDLTDLQ  PYMRQFVAHL QETSPLRDAV VIEQSSSLNE       810        820         830        840        850ASSGLFDVFL MFMCHHAVRI  RGKSYVQCQG IPQGSILSTD LCSLCYMDME       860        870         880        890        900NKLFAGIRRD GLLLRLQYIK ANSKEFIGITE LFLLVRPHLT HAKTFLRTLV       910        920         930        940        950RGVPEYGCVV NLRKTVVNFP  VEDEALGGTA FVQMPAHGLF PWCGLLLDTR       960        970         980        990       1000TAEVQSDYSS YARTSIRASL  TFNRGFKAGR NMRRKLFGVL RLMCHSLFLD      1010       1020        1030       1040       1050LQVNSLQTYC TNIYKILLLQ  AYRFHACVLQ LYFHQQVWKN PTFFLRVISD      1060       1070        1080       1090       1100TASLCYSILK AKNAGMSLGA  KGAAGPLPSE AVQWLCHQAF LLKLTRHRVT      1110        112        1130       1140YVPLLGSLRT AQTQLSRKLP  GTTLTALEAA ANPALPSDFK TILD

What is claimed is:
 1. An altered human telomerase polypeptide with atleast 90% identity to the sequence set forth in any one of SEQ ID NOs:28 or 29, wherein the altered human telomerase polypeptide is notidentical to SEQ ID NO:
 1. 2. The altered human telomerase polypeptideof claim 1, wherein the altered human telomerase polypeptide comprisesan insertion of a non-human T cell helper epitope into the polypeptidesequence of the altered human telomerase, wherein the non-human T cellhelper epitope binds more than one human class II HLA type.
 3. Thealtered human telomerase polypeptide of claim 1 encoded by apolynucleotide.
 4. The altered human telomerase polynucleotide of claim3, wherein the polynucleotide comprises ribonucleic acid (RNA).
 5. Thealtered human telomerase polypeptide of claim 1, wherein at least eightcontiguous amino acids of the polypeptide is bound to a cell surfacehuman leukocyte antigen of an antigen presenting cell.
 6. The alteredhuman telomerase polypeptide of claim 1, further comprising animmunological adjuvant.
 7. A polypeptide comprising at least twosequences from SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ IDNO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ IDNO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ IDNO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ IDNO: 26, or SEQ ID NO:
 27. 8. The polypeptide of claim 7, comprising atleast seven different sequences from SEQ ID NO:2, SEQ ID NO:3, SEQ IDNO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9,SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14,SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19,SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO: 24,SEQ ID NO: 25, SEQ ID NO: 26, or SEQ ID NO: 27, wherein each of theseven different sequences binds a different human leukocyte antigenselected from the group consisting of A1, A2, A3, A11, A24, B3, B7, andB44.
 9. The polypeptide of claim 7, comprising a non-human T cell helperepitope, wherein the non-human T cell helper epitope binds more than onehuman class II HLA type.
 10. The polypeptide of claim 7, wherein thepolypeptide comprises a total length of at least 20 amino acids.
 11. Thepolypeptide of claim 7 encoded by a polynucleotide.
 12. Thepolynucleotide of claim 11, wherein the polynucleotide comprisesribonucleic acid (RNA).
 13. The polypeptide of claim 7, wherein at leasteight contiguous amino acids of the polypeptide is bound to a cellsurface human leukocyte antigen of an antigen presenting cell.
 14. Thepolypeptide of claim 7, further comprising an immunological adjuvant.15. An altered human telomerase polypeptide with at least 90% identityto the sequence set forth in SEQ ID NO: 1, wherein the altered humantelomerase polypeptide comprises at least one amino acid substitutionthat is at position R19, L22, R132, L152, D444, K492, E555, L556, T564,R572, R577, D637, L675, E727, R742, T765, R811, L840, G847, T874, L940,K981, V997, or P1020.
 16. The altered human telomerase polypeptide ofclaim 15, wherein the altered human telomerase polypeptide comprises aninsertion of a non-human T cell helper epitope into the polypeptidesequence of the altered human telomerase, wherein the non-human T cellhelper epitope binds more than one human class II HLA type.
 17. Thepolypeptide of claim 15 encoded by a polynucleotide.
 18. The alteredhuman telomerase polynucleotide of claim 17, wherein the polynucleotidecomprises ribonucleic acid (RNA).
 19. The altered human telomerasepolypeptide of claim 15, wherein at least eight contiguous amino acidsof the polypeptide is bound to a cell surface human leukocyte antigen ofan antigen presenting cell.
 20. The altered human telomerase polypeptideof claim 15, further comprising an immunological adjuvant.